Asymmetric synthesis and applications of α-aryl triketopiperazines

This project aims to explore the asymmetric synthesis of α-aryl triketopiperazines and their application in synthetic transformations to access biologically relevant scaffolds. Chapter One provides a brief overview of the triketopiperazine motif including initial manipulations and its occurrence in nature. Recent work from our research group has demonstrated that triketopiperazines can undergo highly enantioselective Michael additions. Chapter Two provides an overview of these publications and the extension of this methodology to α-aryl triketopiperazines, including their synthesis and participation in asymmetric organocatalytic Michael additions. Further investigations into the transformation of the Michael addition products towards biologically relevant scaffolds are discussed in Chapter Three. This includes a novel method for access to an unusual diazabicycle and its further transformations. The application of methodology for access to quaternary α-amino acids from triketopiperazines, developed within our research group in collaboration with AstraZeneca, is discussed in Chapter Four. Chapter Five explores the triketopiperazine core as a vehicle for access to natural product scaffolds and the synthesis of a natural product possessing a triketopiperazine is also discussed